Baby TCD is a proposed ancillary study to the initial phase of Baby HUG, a multicenter clinical trial funded by NHLBI/NIH (Contract No. N01-HB-07160). In Baby HUG, infants (12-17 months old) with sickle cell disease (SCD) will be randomized to either hydroxyurea (HU) or placebo and followed for 24 months. There is broad interest in the effect of HU on the central nervous system in the children being studied. Stroke occurs after age 1 year and there is evidence that the process of cerebrovascular disease starts very early in some patients. The Cooperative Study of Sickle Cell Disease documented a high risk of incident stroke in the 2-6 year age group. This ancillary study proposes to explore how HU might work by using transcranial Doppler (TCD) ultrasound as a biomarker of stroke risk. The proposed study will perform TCD on the 40 children in Baby HUG at baseline and at end of study. TCD has proven very useful in estimation of stroke risk in children with SCD ages 2-16 years, and is at the center of a paradigm of primary stroke prevention recommended by NHLBI based on the STOP study. If stroke risk could be detected at an earlier stage (i.e., younger than the 2-16 year-old subjects in STOP), then physicians would be able to provide preventive treatment at an earlier stage of the disease. TCD will be performed before and after 24 months of treatment. TCD performance and reading will be centrally controlled and STOP-consistent. The proposers have experience in TCD of infants, the age targeted by the parent study. TCD will be compared between HU and control groups, before and after treatment. In addition, the proposers have access to data from over 400 children in the 2-4 year age range from the STOP screening program performed in the mid- to late 1990s. Since these patients were not on HU or transfusion this dataset will be used to give an estimate of the prevalence of high stroke risk without HU treatment, and can be compared to the HU group in Baby HUG, adding another important comparative dimension to the analyses. Although the sample size is purposely small as designed by the parent study, large differences in the prevalence of high-risk patients at the end of treatment could be detected by Baby TCD.